CDDF Multi-stakeholder workshop / November 2018

3rd CDDF Multi-Stakeholder Workshop on

Minimal Residual Disease (AML – CLL)

London, United-Kingdom – 8 & 9 November 2018

The success of new treatment options has transformed the prognosis of many patients with haematological malignancies. Now, median progression-free survival is over five years for many entities and populations.

To ensure a timely and cost-effective assessment of new therapeutic options, there is need for alternative response evaluation methods that allow regulatory assessment of investigational compounds in an earlier time-frame than the traditional endpoints of progression-free survival and overall survival.

Minimal (or rather measurable) residual disease (MRD) has come to the forefront of these efforts as novel therapies achieve high rates of complete remissions by conventional criteria and more sensitive measures are needed to predict long-term outcomes.

The use of MRD in hematologic malignancy trials is rising among other clinical endpoints. In a recent analysis (Gormley N et al., JCO 2017; 35: 2541) nearly 40% of applications submitted to the FDA Division of Hematology Products between 2014 and 2016 included MRD data. While the data submitted was deemed adequate for inclusion in the PI in 46% of cases, 31% of applications contained MRD data that the Agency deemed un-interpretable.

Regulatory agencies have released guidelines that acknowledge the need for alternative endpoints and describe the use of MRD endpoints and what is needed to move further.

CDDF multi-stakeholder workshop on MRD have been held in 2014 (breast cancer and haemotological malignancies) and in 2017 (Multiple Myeloma) and have generated useful discussions and reports for the further development of the field (cddf.org).

In Acute Myeloid Leukemia (AML) and in Chronic Lymphatic Leukemia (CLL) new data and scientific guidelines have moved the field forward and warrant an updated discussion

This workshop focused on current status and next steps for the use MRD in AML and CLL clinical trials as well as on open exchange, learning and collaborative search for agreements from regulatory, academic and industry perspectives.

The topics discussed were: review of the AML and CLL MRD landscape by leading academic researchers; recent developments of clinical and methodological aspects (incl. method validation); current status of EMA and FDA regulatory thinking; how to use MRD as an endpoint in pivotal clinical trials and subsequent regulatory pathways; next steps relevant for all stakeholders.